Interpret pedigrees to deduce patterns of inheritance (autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive) and calculate the probability of specified offspring genotypes and phenotypes

What this dot point is asking

QCAA wants you to read a pedigree, decide the most likely inheritance pattern from the clues in the chart, and calculate probabilities for specified offspring. Pedigree questions are standard exam fare and reward systematic elimination.

The answer

A pedigree is a family tree showing the phenotype (and sometimes genotype) of each individual. By the patterns the trait makes across generations, you can usually distinguish autosomal dominant, autosomal recessive, X-linked dominant and X-linked recessive inheritance, and then calculate probabilities for future children.

Pedigree symbols and conventions

• Squares represent males, circles females.
• Filled (shaded) symbols are affected; unfilled are unaffected.
• A horizontal line between two symbols shows a mating pair.
• A vertical line from a pair leads down to their offspring, joined by a horizontal sibship line. Offspring are drawn left to right by birth order.
• Generations are labelled with Roman numerals (I, II, III) on the left margin. Individuals are numbered with Arabic numerals (1, 2, 3) within each generation. So III-2 is the second person in generation III.
• A diagonal line through a symbol indicates the individual is deceased. A dot inside an unfilled symbol can indicate a known carrier. A double horizontal line indicates a consanguineous (related) mating.

The four common inheritance patterns

For each, look for diagnostic features.

Autosomal dominant.

• Appears in every generation. Does not skip.
• An affected child usually has at least one affected parent.
• Males and females affected in roughly equal numbers.
• Affected fathers can pass to sons (so father to son transmission is possible, unlike X-linked).
• Examples: Huntington's disease, achondroplasia, neurofibromatosis type 1.

Autosomal recessive.

• Skips generations. Two unaffected (carrier) parents can have affected children.
• Males and females affected in roughly equal numbers.
• More common in offspring of consanguineous matings.
• Examples: cystic fibrosis, phenylketonuria, Tay-Sachs disease.

X-linked dominant.

• Affects both sexes, usually females about twice as often as males (because females have two X chromosomes).
• An affected father passes the trait to all his daughters and none of his sons. This is the hallmark.
• Affected mothers pass to about half their sons and half their daughters.
• Does not skip generations.
• Examples: hypophosphatemic rickets, fragile X (with caveats).

X-linked recessive.

• Affects mainly males. Females are rarely affected (need to be homozygous).
• Skips generations through carrier females.
• An affected father cannot pass the trait to his son (sons get the Y, not the X).
• An affected male passes the carrier allele to all his daughters; his daughters' sons have a 50 per cent chance of being affected.
• Examples: haemophilia A and B, red-green colour blindness, Duchenne muscular dystrophy.

Y-linked (holandric). Rare. Passes father to son only. Affects only males.

Elimination strategy

Work through the pedigree systematically.

• Dominant or recessive? Look at offspring of unaffected parents. If they have any affected child, the trait is recessive (and both parents are carriers). If every affected child has an affected parent, the trait is more likely dominant.
• Autosomal or X-linked? Look at affected fathers and their sons. If an affected father has affected sons (and the trait is dominant), it must be autosomal (because X-linked dominant fathers pass the X only to daughters). Conversely, for a recessive trait, count affected females (rare in X-linked recessive). A single affected female with an unaffected father rules X-linked recessive out.

Probability calculations

Once you know the inheritance pattern and parental genotypes, use the same Punnett square logic as Mendelian inheritance.

Rules.

• Product rule. For two independent events both occurring, multiply their probabilities. P(affected and boy) equals P(affected) x P(boy).
• Sum rule. For mutually exclusive events, add their probabilities. P(affected boy or affected girl) equals P(affected and boy) plus P(affected and girl) equals P(affected).
• Conditional probability. If you are told the offspring is unaffected, recalculate using only the unaffected outcomes. For Cc x Cc, given that the child is unaffected, the chance they are a carrier is 2/3 (two carrier outcomes among three unaffected outcomes), not 1/2.

Worked example. Two carriers Cc x Cc. What is the probability the next two children are both affected (cc) girls?

• P(cc) per child equals 1/4.
• P(girl) per child equals 1/2.
• P(affected girl) per child equals 1/4 x 1/2 equals 1/8.
• P(two affected girls in a row) equals 1/8 x 1/8 equals 1/64.

Identifying carriers

In an autosomal recessive pedigree, an unaffected child of two carriers has a 2/3 chance of being a carrier (given they are unaffected). This is a common stumbling block: do not just halve the 1/2 carrier offspring probability without conditioning on the observation.

Common traps

Reading pedigree symbols incorrectly. Squares are male, circles female. Filled means affected.

Assuming a single example confirms the pattern. Look for the pattern across several families or generations.

Forgetting father to son transmission rules out X-linkage. This is the single fastest way to eliminate an X-linked model.

Confusing the product and sum rules. Use product for "and" with independent events; use sum for "or" with mutually exclusive events.

Forgetting to condition on observed information. An unaffected sibling of an affected child does not have a 2/4 chance of being a carrier; given that they are unaffected, they have a 2/3 chance.

In one sentence

Pedigree analysis identifies the most likely inheritance pattern by checking whether the trait skips generations (recessive) or persists in every generation (dominant), and whether it affects males more than females or shows father to son transmission (autosomal versus X-linked), and once the pattern is established the probability of any specified offspring is calculated by combining the Mendelian Punnett-square ratios with the product rule for independent events (such as genotype and sex) and the sum rule for mutually exclusive outcomes.